Method and system for providing basal profile modification in analyte monitoring and management systems

ABSTRACT

Method and system for providing basal profile modification in insulin therapy for use with infusion devices includes periodically monitoring the analyte levels of a patient for a predetermined period of time in order to determine, based on the monitored analyte levels, an appropriate modification factor to be incorporated into the underlying basal profile which was running at the time the periodic monitoring of the analyte levels were performed.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of U.S. patent applicationSer. No. 15/880,692, filed Jan. 26, 2018, which is a continuation ofU.S. patent application Ser. No. 15/613,713, filed Jun. 5, 2017, nowU.S. Pat. No. 9,669,162, which is a continuation of U.S. patentapplication Ser. No. 15/071,610, filed Mar. 16, 2016, now U.S. Pat. No.9,669,162, which is a continuation of U.S. patent application Ser. No.14/081,737, filed Nov. 15, 2013, now U.S. Pat. No. 9,323,898, which is acontinuation of U.S. patent application Ser. No. 12/833,975, filed Jul.10, 2010, now U.S. Pat. No. 8,585,591, which is a continuation of U.S.patent application Ser. No. 11/267,724, filed Nov. 4, 2005, now U.S.Pat. No. 7,766,829, the disclosures of all of which are incorporatedherein by reference in their entireties for all purposes.

BACKGROUND

The present invention relates to analyte monitoring systems and healthmanagement systems. More specifically, the present invention relates tomethod and system for providing basal profile modification in analytemonitoring systems to improve insulin therapy in diabetic patients.

In data communication systems such as continuous, semi-continuous ordiscrete analyte monitoring systems for insulin therapy, analyte levelsof a patient are monitored and/or measured, and the measured analytelevels are used for treatment. For example, real time values of measuredanalyte levels of a patient would allow for a more robust and accuratediabetes treatment. Moreover, a profile of a series of measured analytelevels of a diabetic patient can provide valuable information regardingthe fluctuations and variations of the analyte levels in a diabeticpatient. In turn, this type of information would be invaluable inestablishing a suitable insulin therapy regimen.

Many diabetic patients that use an infusion device such as an infusionpump generally have preset or pre-established basal profiles which areprogrammed or stored into the infusion device by the patient's physicianor the patient herself Indeed, based on several factors such as insulinsensitivity, the patient's physiology and other variable factors thataffect the patient's analyte levels, the physician may tailor the basalprofiles of the patient to be programmed into the infusion device suchthat the patient's analyte level is maintained within an acceptablerange, and thus the patient is not going to experience hyperglycemia orhypoglycemia.

While physicians attempt to best determine the most suitable basalprofiles for each diabetic patient using the infusion device, it isoften difficult to attain the most suitable profiles to ensure the safeoperating range of the infusion device while providing the patient withthe most suitable level of insulin at all times when the patient iswearing and operating the infusion device.

Often, diabetics who use infusion pumps run basal profiles to maintain asteady level of insulin and also, supplement with additional bolusesadministered typically with the same infusion pumps. Various devicesexist that enable the determination of the appropriate bolus tosupplement the basal profiles. For example, prior to the ingestion of alarge quantity of carbohydrates, the patient is able to calculate acarbohydrate bolus and administer the same with the infusion pump sothat the intake of the carbohydrates does not adversely impact thepatient's physiology. While bolus supplements are useful and critical toa well managed insulin therapy regimen, it does not address theunderlying concern related to the basal profiles that the infusiondevices are programmed to administer.

In view of the foregoing, it would be desirable to have a method andsystem for providing basal profile modification for diabetic patients soas to comprehend each patient's unique physiology as well as response toinsulin intake. More specifically, it would be desirable to modify basalprofiles such that as the use of the infusion device progresses, thepatient's basal profiles may be tailored to be more suitable for thatpatient.

SUMMARY OF THE INVENTION

In accordance with the various embodiments of the present invention,there is provided a method and system for analyte monitoring andmanagement configured to monitor the levels of a patient's analyte overa predetermined period of time, and based on the monitored analytelevels, determine one or more patterns in the analyte levels for thegiven period of time, and to provide a recommendation for modificationto the basal profiles under which a medication delivery system such asan infusion pump is operating.

For example, in one embodiment, the analyte monitoring and managementsystem of the present invention will be configured to monitor theanalyte levels of a patient over a predetermined time period (forexample, 1 day, 3 days, or 7 days), and during which, the patient isusing an infusion device such as an insulin pump administering insulinbased on a predetermined one or more basal profiles. Upon conclusion ofthe analyte level monitoring during the predetermined time period, thecollected data are analyzed and, considered in conjunction with theunderlying basal profiles under which the patient was infusing insulinduring that same predetermined time period, used to determine a suitablemodification to the basal profiles, if any, to improve the insulintherapy of the patient.

In this manner, a robust health management system may be provided whichmay be configured in one embodiment to monitor the analyte levels of apatient over a period of time and to recommend or suggest a modificationto the existing or current basal profiles based on the collected andanalyzed analyte levels taken in conjunction with the underlying basalprofiles under which the infusion device was running during the timeperiod of analyte level monitoring. Within the scope of the presentinvention, the monitored time period may vary depending upon thepatient's need, the underlying basal profiles, the condition of thepatient and the like, such that the patient may alter or modify therunning basal profiles prior to its completion based on the monitoredand analyzed analyte levels so as to provide a more effective insulintherapy.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates a block diagram of a data monitoring and managementsystem for practicing one embodiment of the present invention;

FIG. 2 is a block diagram of the transmitter unit of the data monitoringand management system shown in FIG. 1 in accordance with one embodimentof the present invention;

FIG. 3 is a flowchart illustrating the process for monitoring analytelevels and determining modification to a current basal profile inaccordance with one embodiment of the present invention; and

FIGS. 4A-4C illustrate a current basal profile, a monitored analytelevel profile, and a modified basal profile recommendation respectively,in accordance with one embodiment of the present invention.

DETAILED DESCRIPTION

FIG. 1 illustrates a data monitoring and management system such as, forexample, an analyte (e.g., glucose) monitoring and management system 100in accordance with one embodiment of the present invention. The subjectinvention is further described primarily with respect to an analytemonitoring and management system for convenience and such description isin no way intended to limit the scope of the invention. It is to beunderstood that the analyte monitoring system may be configured tomonitor a variety of analytes, e.g., lactate, and the like.

Indeed, analytes that may be monitored include, for example, acetylcholine, amylase, bilirubin, cholesterol, chorionic gonadotropin,creatine kinase (e.g., CK-MB), creatine, DNA, fructosamine, glucose,glutamine, growth hormones, hormones, ketones, lactate, peroxide,prostate-specific antigen, prothrombin, RNA, thyroid stimulatinghormone, and troponin. The concentration of drugs, such as, for example,antibiotics (e.g., gentamicin, vancomycin, and the like), digitoxin,digoxin, drugs of abuse, theophylline, and warfarin, may also bemonitored.

The analyte monitoring and management system 100 includes a sensor 101,a transmitter unit 102 coupled to the sensor 101, and a receiver unit104 which is configured to communicate with the transmitter unit 102 viaa communication link 103. The receiver unit 104 may be furtherconfigured to transmit data to a data processing terminal 105 forevaluating the data received by the receiver unit 104 via communicationlink 106 which may optionally be configured for bi-directionalcommunication. Moreover, the data processing terminal in one embodimentmay be configured to receive data directly from the transmitter unit 102via a communication link 107 which may optionally be configured forbi-directional communication.

Only one sensor 101, transmitter unit 102, receiver unit 104, and dataprocessing terminal 105 are shown in the embodiment of the analytemonitoring and management system 100 illustrated in FIG. 1 . However, itwill be appreciated by one of ordinary skill in the art that the analytemonitoring and management system 100 may include one or more sensor 101,transmitter unit 102, receiver unit 104, and data processing terminal105, where each receiver unit 104 is uniquely synchronized with arespective transmitter unit 102. Moreover, within the scope of thepresent invention, the sensor 101 may include a subcutaneous analytesensor, a transcutaneous analyte sensor, an implantable analyte sensor,or a noninvasive analyte sensor such as a transdermal patch or anoptical sensor (for example, infrared sensor).

Moreover, within the scope of the present invention, the analytemonitoring system 100 may be a continuous monitoring system, orsemi-continuous, or a discrete monitoring system. Additionally, withinthe scope of the present invention, the sensor 101 may include asubcutaneous analyte sensor or an implantable analyte sensor which isconfigured to be substantially wholly implanted in a patient.

In one embodiment of the present invention, the sensor 101 is physicallypositioned in or on the body of a user whose analyte level is beingmonitored. The sensor 101 may be configured to continuously sample theanalyte level of the user and convert the sampled analyte level into acorresponding data signal for transmission by the transmitter unit 102.In one embodiment, the transmitter unit 102 is mounted on the sensor 101so that both devices are positioned on the user's body. The transmitterunit 102 performs data processing such as filtering and encoding on datasignals, each of which corresponds to a monitored analyte level of theuser, for transmission to the receiver unit 104 via the communicationlink 103.

In one embodiment, the analyte monitoring system 100 is configured as aone-way RF communication path from the transmitter unit 102 to thereceiver unit 104. In such embodiment, the transmitter unit 102transmits the sampled data signals received from the sensor 101 withoutacknowledgement from the receiver unit 104 that the transmitted sampleddata signals have been received. For example, the transmitter unit 102may be configured to transmit the encoded sampled data signals at afixed rate (e.g., at one minute intervals) after the completion of theinitial power on procedure. Likewise, the receiver unit 104 may beconfigured to detect such transmitted encoded sampled data signals atpredetermined time intervals. Alternatively, the analyte monitoringsystem 100 may be configured with a bi-directional RF (or otherwise)communication between the transmitter unit 102 and the receiver unit104.

Additionally, in one aspect, the receiver unit 104 may include twosections. The first section is an analog interface section that isconfigured to communicate with the transmitter unit 102 via thecommunication link 103. In one embodiment, the analog interface sectionmay include an RF receiver and an antenna for receiving and amplifyingthe data signals from the transmitter unit 102, which are thereafter,demodulated with a local oscillator and filtered through a band-passfilter. The second section of the receiver unit 104 is a data processingsection which is configured to process the data signals received fromthe transmitter unit 102 such as by performing data decoding, errordetection and correction, data clock generation, and data bit recovery.

In operation, upon completing the power-on procedure, the receiver unit104 is configured to detect the presence of the transmitter unit 102within its range based on, for example, the strength of the detecteddata signals received from the transmitter unit 102 or a predeterminedtransmitter identification information. Upon successful synchronizationwith the corresponding transmitter unit 102, the receiver unit 104 isconfigured to begin receiving from the transmitter unit 102 data signalscorresponding to the user's detected analyte level. More specifically,the receiver unit 104 in one embodiment is configured to performsynchronized time hopping with the corresponding synchronizedtransmitter unit 102 via the communication link 103 to obtain the user'sdetected analyte level.

Referring again to FIG. 1 , the data processing terminal 105 in oneembodiment may be configured to include a medication delivery unit suchas an infusion device including, for example, an insulin pump, and whichmay be operatively coupled to the receiver unit 104. In such anembodiment, the medication delivery unit 105 may be configured toadminister a predetermined or calculated insulin dosage based on theinformation received from the receiver unit 104. For example, asdiscussed in further detail below, the medication delivery unit 105 inone embodiment may be configured to deliver insulin based onpre-programmed basal profiles to diabetic patients, as well as todetermine and/or administer one or more suitable bolus levels (e.g.,carbohydrate bolus, and correction bolus).

Referring again to FIG. 1 , the receiver unit 104 may include a personalcomputer, a portable computer such as a laptop or a handheld device(e.g., personal digital assistants (PDAs)), and the like, each of whichmay be configured for data communication with the receiver via a wiredor a wireless connection. Additionally, the receiver unit 104 mayfurther be connected to a data network (not shown) for storing,retrieving and updating data corresponding to the monitored analytelevels of the patient.

Furthermore, in one embodiment of the present invention, the receiverunit 104 or the data processing terminal 105, or both the receiver unit104 and the data processing terminal 105 may be configured toincorporate a glucose strip meter so as to be configured to include, forexample, a test strip port for receiving a glucose test strip. In thisembodiment of the present invention, the receiver unit 104 and the dataprocessing terminal 105 may be configured to perform analysis upon thesample from the glucose test strip so as to determine the glucose levelfrom the test strip. One example of such strip meter is Freestyle®glucose meters commercially available from the assignee of the presentinvention, Abbott Diabetes Care Inc. of Alameda Calif.

Furthermore, within the scope of the present invention, the dataprocessing terminal 105 may include an infusion device such as aninsulin infusion pump or the like, which may be configured to administerinsulin to patients, and which may be configured to communicate with thereceiver unit 104 for receiving, among others, the measured glucoselevel. Alternatively, the receiver unit 104 may be configured tointegrate an infusion device therein so that the receiver unit 104 isconfigured to administer insulin therapy to patients, for example, foradministering and modifying basal profiles, as well as for determiningappropriate boluses for administration based on, among others, thedetected analyte levels received from the transmitter unit 102.

Additionally, the transmitter unit 102, the receiver unit 104 and thedata processing terminal 105 may each be configured for bi-directionalwireless communication such that each of the transmitter unit 102, thereceiver unit 104 and the data processing terminal 105 may be configuredto communicate (that is, transmit data to and receive data from) witheach other via the wireless communication link 103. More specifically,the data processing terminal 105 may in one embodiment be configured toreceive data directly from the transmitter unit 102 via thecommunication link 106, where the communication link 106, as describedabove, may be configured for bi-directional communication. In thisembodiment, the data processing terminal 105 which may include aninsulin pump, may be configured to receive the analyte signals from thetransmitter unit 102, and thus, incorporate the functions of thereceiver 104 including data processing for managing the patient'sinsulin therapy and analyte monitoring.

In one embodiment, the communication link 103 may include one or more ofan RF communication protocol, an infrared communication protocol, aBluetooth® enabled communication protocol, an 802.11x wirelesscommunication protocol, or an equivalent wireless communication protocolwhich would allow secure, wireless communication of several units (forexample, per HIPAA requirements) while avoiding potential data collisionand interference.

FIG. 2 is a block diagram of the transmitter of the data monitoring anddetection system shown in FIG. 1 in accordance with one embodiment ofthe present invention. Referring to the Figure, the transmitter 102 inone embodiment includes an analog interface 201 configured tocommunicate with the sensor 101 (FIG. 1 ), a user input 202, and atemperature measurement section 203, each of which is operativelycoupled to a transmitter processor 204 such as a central processing unit(CPU). As can be seen from FIG. 2 , there are provided four contacts,three of which are electrodes—work electrode (W) 210, guard contact (G)211, reference electrode (R) 212, and counter electrode (C) 213, eachoperatively coupled to the analog interface 201 of the transmitter 102for connection to the sensor unit 101 (FIG. 1 ). In one embodiment, eachof the work electrode (W) 210, guard contact (G) 211, referenceelectrode (R) 212, and counter electrode (C) 213 may be made using aconductive material that is either printed or etched, for example, suchas carbon which may be printed, or metal foil (e.g., gold) which may beetched.

Further shown in FIG. 2 are a transmitter serial communication section205 and an RF transmitter 206, each of which is also operatively coupledto the transmitter processor 204. Moreover, a power supply 207 such as abattery is also provided in the transmitter 102 to provide the necessarypower for the transmitter 102. Additionally, as can be seen from theFigure, clock 208 is provided to, among others, supply real timeinformation to the transmitter processor 204.

In one embodiment, a unidirectional input path is established from thesensor 101 (FIG. 1 ) and/or manufacturing and testing equipment to theanalog interface 201 of the transmitter 102, while a unidirectionaloutput is established from the output of the RF transmitter 206 of thetransmitter 102 for transmission to the receiver 104. In this manner, adata path is shown in FIG. 2 between the aforementioned unidirectionalinput and output via a dedicated link 209 from the analog interface 201to serial communication section 205, thereafter to the processor 204,and then to the RF transmitter 206. As such, in one embodiment, via thedata path described above, the transmitter 102 is configured to transmitto the receiver 104 (FIG. 1 ), via the communication link 103 (FIG. 1 ),processed and encoded data signals received from the sensor 101 (FIG. 1). Additionally, the unidirectional communication data path between theanalog interface 201 and the RF transmitter 206 discussed above allowsfor the configuration of the transmitter 102 for operation uponcompletion of the manufacturing process as well as for directcommunication for diagnostic and testing purposes.

As discussed above, the transmitter processor 204 is configured totransmit control signals to the various sections of the transmitter 102during the operation of the transmitter 102. In one embodiment, thetransmitter processor 204 also includes a memory (not shown) for storingdata such as the identification information for the transmitter 102, aswell as the data signals received from the sensor 101. The storedinformation may be retrieved and processed for transmission to thereceiver 104 under the control of the transmitter processor 204.Furthermore, the power supply 207 may include a commercially availablebattery.

The transmitter 102 is also configured such that the power supplysection 207 is capable of providing power to the transmitter for aminimum of about three months of continuous operation after having beenstored for about eighteen months in a low-power (non-operating) mode. Inone embodiment, this may be achieved by the transmitter processor 204operating in low power modes in the non-operating state, for example,drawing no more than approximately 1 μA of current. Indeed, in oneembodiment, the final step during the manufacturing process of thetransmitter 102 may place the transmitter 102 in the lower power,non-operating state (i.e., post-manufacture sleep mode). In this manner,the shelf life of the transmitter 102 may be significantly improved.Moreover, as shown in FIG. 2 , while the power supply unit 207 is shownas coupled to the processor 204, and as such, the processor 204 isconfigured to provide control of the power supply unit 207, it should benoted that within the scope of the present invention, the power supplyunit 207 is configured to provide the necessary power to each of thecomponents of the transmitter unit 102 shown in FIG. 2 .

Referring back to FIG. 2 , the power supply section 207 of thetransmitter 102 in one embodiment may include a rechargeable batteryunit that may be recharged by a separate power supply recharging unit sothat the transmitter 102 may be powered for a longer period of usagetime. Moreover, in one embodiment, the transmitter 102 may be configuredwithout a battery in the power supply section 207, in which case thetransmitter 102 may be configured to receive power from an externalpower supply source (for example, a battery) as discussed in furtherdetail below.

Referring yet again to FIG. 2 , the temperature measurement section 203of the transmitter 102 is configured to monitor the temperature of theskin near the sensor insertion site. The temperature reading is used toadjust the analyte readings obtained from the analog interface 201. TheRF transmitter 206 of the transmitter 102 may be configured foroperation in the frequency band of 315 MHz to 322 MHz, for example, inthe United States. Further, in one embodiment, the RF transmitter 206 isconfigured to modulate the carrier frequency by performing FrequencyShift Keying and Manchester encoding. In one embodiment, the datatransmission rate is 19,200 symbols per second, with a minimumtransmission range for communication with the receiver 104.

Referring yet again to FIG. 2 , also shown is a leak detection circuit214 coupled to the guard contact (G) 211 and the processor 204 in thetransmitter 102 of the data monitoring and management system 100. Theleak detection circuit 214 in accordance with one embodiment of thepresent invention may be configured to detect leakage current in thesensor 101 to determine whether the measured sensor data is corrupt orwhether the measured data from the sensor 101 is accurate.

Additional detailed description of the continuous analyte monitoringsystem, its various components including the functional descriptions ofthe transmitter are provided in U.S. Pat. No. 6,175,752 issued Jan. 16,2001 entitled “Analyte Monitoring Device and Methods of Use”, and inapplication Ser. No. 10/745,878 filed Dec. 26, 2003 entitled “ContinuousGlucose Monitoring System and Methods of Use”, each assigned to theAssignee of the present application, and the disclosures of each ofwhich are incorporated herein by reference for all purposes.

FIG. 3 is a flowchart illustrating the process for monitoring analytelevels and determining modification to a current basal profile inaccordance with one embodiment of the present invention. Referring toFIG. 3 , at step 301, the analyte levels such as the patient's analytelevel is monitored for a predetermined period of time, and at step 302,the monitored analyte levels are stored in a data storage unit (forexample, in one or more memory devices of the receiver unit 104 and/orthe data processing terminal 105 (FIG. 1 )). Thereafter, at step 303,patient specific parameters are retrieved from the data processingterminal 105 and/or the receiver unit 104, as well as the current basalprofile(s) which the patient is implementing to operate the infusiondevice for insulin delivery during the time period of the analytemonitoring discussed above.

In one embodiment, patient specific parameters may include the type ofinsulin currently being infused into the patient, the patient's insulinsensitivity, insulin resistance level, level of insulin on board, thespecific time period of the analyte monitoring, including the activitiesperformed by the patient during that time period, or any other factorsand variables that may have an impact upon the effectiveness of insulintherapy for the patient.

Referring to FIG. 3 , after retrieving the patient specific parametersand the current basal profile(s) that the patient is implementing in theinfusion device at step 303, at step 304, the monitored analyte levelsare retrieved and, based on one or more patterns from the analyte levelsmonitored and factoring in the current basal profile(s), arecommendation or modification to the current basal profile(s) isdetermined. Thereafter, the recommendation or modification to thecurrent basal profile(s) determined at step 304 is provided to thepatient visually on a display or audibly, or a combination of visual andaudio output, such that the patient may be able to decide whether themodification to the current basal profile(s) is appropriate or suitableto the patient.

While the modification to the basal profile(s) is discussed above asoutput to the patient, within the scope of the present invention, thebasal profile modification determined in accordance with one embodimentof the present invention may be provided to a health care provider so asto determine suitability of the modification to the current basalprofile in view of the monitored analyte levels. Furthermore, in analternate embodiment, the determined modification to the current basalprofile may be provided to both the patient and the healthcare providerso that the patient is able to make an informed decision as to whetherthe recommended modification to the current basal profile is suitablefor the patient in improving insulin therapy to better manage diabetes.

Within the scope of the present invention, the modification to thecurrent basal profile may include several factors that are consideredincluding, for example, the current basal profile as a function of thetime period during which insulin infusion takes place and analyte levelsare monitored, the level of the analyte monitored as a function of time,patient specific parameters discussed above including, for example,patient's activities during the monitored time period, patient's diet,insulin sensitivity, level of insulin on board, and the insulin type,and the frequency of bolus dosing during the time period of the analytelevel monitoring (for example, the number of correction bolus dosing,and/or carbohydrate dosing).

In this manner, in one embodiment of the present invention, themodification to the current basal profile(s) may be achieved for one ormore specific goals for the patient's diabetes management, including forexample, elimination of extreme glucose excursions, automating orsemi-automating routine or regular bolus dosing, and adjustment to themean glucose value.

For example, to effectively eliminate extreme glucose excursions, themodification to the current basal profiles may be configured to providerecommendation to modify to reduce extreme levels, so that unless themonitored glucose level exceeds a predetermined threshold level (e.g,200 mg/dL), modification to the current basal profile is notrecommended. In the case of automating regular bolus dosing, based onthe monitored analyte levels, a regular correction bolus dosing duringthe current basal profile implementation may be converted into amodification to the current basal profile so that the patient mayeffectively be rid of the need to implement routine correction typebolus dosing. Additionally, with the collected data from thecontinuously monitored analyte levels, the current basal profile may bemodified to adjust the mean target glucose value even in the case whereextreme excursions of glucose levels do not occur.

Within the scope of the present invention, the current basal profilemodification may be performed at different times during the time thatthe patient is using an infusion device. For example, the patient mayperform the current basal profile modification procedure discussed aboveon a daily basis if, for example, glucose excursions are anticipated ona regular basis. Alternatively, the current basal profile modificationprocedure may be performed each time a bolus is administered.

Moreover, within the scope of the present invention, when a pattern ofglucose excursions is detected over several days (for example, 48 or 72hours), the analyte monitoring and management system 100 (FIG. 1 ) maybe configured to continue analyte level monitoring to determine whethera pattern exists in the frequency and/or level of the glucoseexcursions. In such a case, it is possible to modify the current basalprofile modification procedure to correct for such patterns in themonitored analyte levels such that the modification to the current basalprofile may address such excursions.

In a further embodiment, the loop gain setting may be configured todetermine the appropriate level of modification to the current basalprofiles for a given glucose excursion pattern detected based on themonitored analyte levels. While several iterations may be necessary forlow loop gain to reach the optimal modification level of the currentbasal profile, a conservative and less aggressive modification may berecommended in such cases. For medium loop gain, when criticallycontrolled, the determined recommendation for modification to thecurrent basal profile may be reached based on one iteration, but withthe potential for an increased risk for overshoot and thereby resultingin over-compensation. Notwithstanding, the loop gain setting may betrained into the analyte monitoring and management system 100 so that bystarting with a low loop gain and then learning the loop responses toreach the optimal loop gain, the desired modification to the currentbasal profile may be determined and provided to the patient.

FIGS. 4A-4C illustrate a current basal profile, a monitored analytelevel profile, and a modified basal profile recommendation respectively,in accordance with one embodiment of the present invention. Referring toFIG. 4A, a profile of the glucose level as a function of time is shownfor a current basal profile programmed into the infusion device of thepatient. FIG. 4B illustrates a profile of the glucose levels as afunction of time for the same time period during which the basal profileshown in FIG. 4A is administered to the patient. Finally, FIG. 4Cillustrates a profile of glucose level as a function of time whichfactors in the patient parameters including the monitored glucose levelsof the patient, to provide a modification to the current basal profileso as to improve the patient's insulin therapy.

Indeed, in one embodiment of the present invention, it can be seen thatthe analyte level monitoring and detecting patterns in the monitoredanalyte levels during the time period that the patient is using aninfusion device such as an insulin pump running a pre-programmed basalprofile, provides contemporaneous patient response of the infusedinsulin based on the current basal profile, and thus, it is possible toimprove the insulin therapy.

By way of an example, in the case that the patient desired to eliminateor substantially reduce the occurrences of high glucose extremes orexcursions, it is determined whether there is a consistent pattern ofhigh glucose levels versus time of day of such occurrence based on themonitored glucose levels. An example of such monitored levels is shownin the Table 1 below:

TABLE 1 High Glucose Excursions 00:00 00:30 01:00 01:30 23:30 Day 1(0-24 hr) 1 1 Day 2 (24-48 hr) 1 1 1 Day 3 (48-72 hr) 1 1 1 Sum 2 1 3 20where over a 72 hour period post calibration of the sensor 101 (FIG. 1), the monitored data is reviewed to determine if the monitored glucoselevel exceeds a predetermined threshold level. Each occurrence of whenthe glucose level exceeds a predetermined threshold level is shown witha “1” in Table 1 above.

For each column shown in Table 1 where the sum of the data entry equals“3”, and the sum of the adjacent columns is equal to or greater than“1”, the analyte monitoring and management system 100 in one embodimentmay be configured to recommend an increase to the current basal profilefor that time slot or period during the 72 hour period.

More specifically, using a conventional bolus calculation mechanism, acorrection bolus may be determined based on the detection of the highglucose level. Thereafter, rather than implementing the calculatedcorrection bolus, the modification to the current basal profile may bedetermined based on the following relationship:

Modification=K*Calculated Correction Bolus/30 minutes  (1)

where K is a loop gain value determined by the patient's health careprovider, and is typically less than 1 for over dampened control, andfurther, where the 30 minutes is a scaling factor for the Modificationdetermination.

After the calculation, the determined Modification from the equation (1)above is provided to the patient to either accept and implement, storagefor further analysis or modification, or reject.

In one embodiment, the Modification determination based on relationshipdescribed in the equation (1) above may include glucose rate or higherderivative information, or alternatively, may also include an integralfactor. In a further embodiment, the determination may also factor inthe glucose profile variation. Other potentially relevant factors alsoinclude the physiological dynamics and/or sensor/monitor dynamics, aswell as the patient's insulin infusions, caloric intake, exercise, etc.

As another example, in the case where correction bolus dosing may bereplaced with modification to the current basal profiles based on themonitored analyte levels, a consistent pattern in the monitored analytelevels of bolus delivery versus time of day is determined. Table 2 belowshows one example of such pattern:

TABLE 2 Bolus Replacement 00:00 00:30 01:00 01:30 23:30 Day 1 (0-24 hr)1 1 Day 2 (24-48 hr) 1 1 1 Day 3 (48-72 hr) 1 1 1 Sum 2 1 3 2 0

Referring to Table 2 and in conjunction with equation (1) discussedabove, the administration of bolus doses is reviewed and if, forexample, there were three bolus deliveries (each shown in Table 2 with a“1” entry) within 30 minutes of the same time of day period, then anincrease in the insulin level for same time period may be proposed tothe current basal profile using equation (1) to determine the level ofmodification to the current basal profile.

In the case of addressing the occurrence of low extremes of glucoselevels, similar determinations as above may be performed given themonitored analyte levels for the desired time period and data reviewedfor detection of patterns in the monitored analyte levels associatedwith the occurrences of low extremes. For example, Table 3 belowprovides data for a three day period illustrating patterns associatedwith the occurrences of low extremes.

TABLE 3 Low Extremes Pattern 00:00 00:30 01:00 01:30 23:30 Day 1 (0-24hr) 1 1 Day 2 (24-48 hr) 1 1 1 Day 3 (48-72 hr) 1 1 1 Sum 2 1 3 2 0where the “1” entry in a particular column illustrates the occurrence ofthe measured glucose level that is below a predetermined low thresholdlevel.

Again, in conjunction with equation (1) above, a modification to thecurrent basal profile may be determined and provided to the patient.More specifically, where over a 72 hour period post calibration of thesensor 101 (FIG. 1 ), the monitored data is reviewed to determine if themonitored glucose level falls below the predetermined low thresholdlevel, each such is shown with a “1” in Table 3 above.

For each column shown in Table 3 where the sum of the data entry equals“3”, and the sum of the adjacent columns is equal to or greater than“1”, the analyte monitoring and management system 100 in one embodimentmay be configured to recommend a modification to the current basalprofile for that time slot or period during the 72 hour period based onthe relationship set forth in equation (1). The user or patient may thenbe provided with the modification to the current basal profile which maybe accepted for implementation, stored for further analysis ormodification, or rejected by the patient.

In the case of reducing the mean glucose level using the analytemonitoring and management system 100 in one embodiment of the presentinvention, again, consistent patterns in the monitored analyte levelsover a predetermined time period is analyzed and detected as a functionof time of day of the analyte level monitoring. Table 4 below shows anexample of such pattern:

TABLE 4 Mean Glucose Level 00:00 00:30 01:00 01:30 23:30 Day 1 (0-24 hr)1 1 Day 2 (24-48 hr) 1 1 1 Day 3 (48-72 hr) 1 1 1 Sum 2 1 3 2 0where, an entry of a “1” in Table 4 above illustrates a detected glucoselevel of greater than a predetermined level (e.g., 120) during the threeday period based on the data from the sensor 101 (FIG. 1 ).

Again, similar to the determinations above, if the sum of any column inTable 4 is equal to three, and the sum of the adjacent columns isgreater than or equal to one, then a decrease in the current basalprofile for that particular time slot is recommended based on therelationship set forth above in equation (1).

In a further embodiment, a 24 hour profile may be determined based ontime-of-day averages over a predetermined number of days. The correctionfactor may then be based on maintaining the time-of-day averages withina predetermined target range value. Within the scope of the presentinvention, the various approaches and implementations for correctioncalculation and/or basal profile modification recommendation may becombined or implemented individually, depending upon the patient'sphysiology and the criteria for drug therapy such as insulin therapy.

In accordance with the various embodiments of the present invention,additional or alternative approaches to the determination of themodification to the basal profile may include, for example, (1)modifying the basal rate by a constant value, (2) changing the basalrate by a constant percentage of the current basal profile rate, (3)changing the basal rate in proportion to the magnitude of the error, or(4) changing the basal rate in proportion to the magnitude of the error,compensating for the loop gain factor based on the affects of theprevious basal rate modifications/adjustments. Each of these approacheswithin the scope of the present invention is described in further detailbelow.

In the first embodiment described above, the basal rate is configuredfor modification by a constant amount. For example, the modification isdescribed by the following equation (2):

Modification=sign(measured−target)*U  (2)

-   -   where U is a constant value in insulin units, and is applied to        the difference between the target glucose and measured glucose        levels.

Moreover, the “sign(measured−target)” relationship holds the following:

-   -   if (measured−target)=0, then 0        -   else if (measured−target)>0, then +1        -   else if (measured−target)<0, then −1

For example, in the equation (2) above, the constant value U may be 0.1units of insulin/hour. This may be a configurable value. Indeed, for thecase where U is 0.1 units, if the measured glucose level is 140, whilethe target glucose level is 100, then the Modification to the basal ratewould result in +1*0.1 equaling 0.1 units/hour.

In this manner, in one embodiment, a simple and effective basal ratemodification approach is provided and which does not require knowledgeof the patient's physiology, is simple to implement, and does notprovide resolution issues. On the other hand, for safe values of theconstant factor U, several iterations or corrections may be needed toreach the desired results.

In another embodiment, the basal rate may be modified by a constantpercentage of the current rate. In this case, the following equation (3)holds:

Modification=sign(measured−target)*K*U  (3)

where K=constant percentage, 0<=K<=1, and U=current basal rate(in unitsof insulin).

For example, where the constant percentage K is 0.1 and with the currentbasal rate U of 2.0 units/hour, and for example, the measured and targetglucose levels at 140 and 100, respectively, the basal rate Modificationin accordance with the equation (3) equals +1*0.1*2.0=0.2 units/hour. Inthis manner, in one embodiment, a simple and effective way to implementbasal rate modification is provided, and which does not require theknowledge of the user's physiology. For safe values of the constantpercentage K, several iterations may be needed to reach the desiredlevel of basal rate modification, and resolution issues may potentiallyarise.

In a further embodiment of the present invention, the modification tothe basal rate may be determined by changing the basal rateproportionally to the magnitude of the error. In this case, thefollowing equation (4) holds:

Modification=(measured−target)*K*P  (4)

-   -   where K is the loop gain factor, and for example, K<1 for        dampened control, K=1 for critical control, K>1 for over        control, and further, where P is the patient's physiological        response to insulin (insulin sensitivity).

For example, in the case where the loop gain factor K is 0.75, thepatient's insulin sensitivity P is 0.02 units/mg/dL, and where themeasured and target glucose levels are 140 and 100, respectively, theModification to the basal rate in accordance to equation (4) isdetermined to be (140-100)*0.75*0.02=0.6 units/hour. This approachrequires prior determination of the patient's insulin sensitivity, andmay likely require less iterations or corrective routines to reach thedesired level of basal rate modification for effective treatment.

In still a further embodiment, the modification to the basal rate may bedetermined by changing the basal rate proportionally to the magnitude oferror, and further making adjustment to the loop gain factor based onthe results of the prior basal rate adjustments. For example, thefollowing equation (5) holds:

-   -   with K=f(affect of last adjustment)

Modification=(measured−target)*K*P  (5)

where K is loop gain factor, and P is the patient's physiology responseto insulin (insulin sensitivity).

For example, if the loop gain factor is initially 0.75, then thedetermined basal rate modification is the same as in the embodimentdescribed above in conjunction with equation (4). In the next iteration,with the measured glucose level still higher than the target level, theloop gain factor is increased. In this case, for example, with measuredglucose level of 110 where the target level is 100, the new loop gainfactor K is determined to be ((first delta)/(first change))*oldK=(40/30)*0.75=1.00.

Having determined the new loop gain factor K, the basal ratemodification is determined by equation (5) as (110-100)*1.00*0.02=0.2units/hour. It is to be noted that if the loop gain factor K did notchange between the two iterations described above, then the basal ratemodification in the second iteration may be relatively smaller, and itcan be seen that the adjustment to the loop gain factor allows fastersettling to the final value. For example, using equation (5) above, thebasal rate modification is determined as:

Modification=(110−100)*0.75*0.02=0.15 units/hour

In this manner, in one embodiment of the present invention, the basalrate modification may be configured to self adjust to the patient'sphysiology such that it may be more tolerant of inaccurate input values.

In this manner, the various embodiments of the present inventionprovides a mechanism for diabetic patients to compare the actual glucoselevels during a predetermined time period and to use that information inaddition to the actual basal profile to recommend a new or modifiedbasal profile to the patient. The patient will have the option to acceptthe recommendation, to accept the recommendation with the modification,or alternatively to decline the proposed modified basal profile so as toselect the most appropriate basal profile for the patient.

Moreover, contrasting with real time closed loop insulin therapy wherethe insulin infusion is modified at a rate (i.e., minutes) much fasterthan the physiological response times, one embodiment of the presentinvention is characterized by a) corrections to basal profiles that aremade over periods (i.e., days) which are much longer than physiologicalresponse times, and b) corrections based on repeating diurnal glucosepatterns. In this manner, in one embodiment, the present invention isconfigured to identify the patient's glucose levels retrospectively overa predetermined period of time (for example, over a 24 hour period) todetermine any recommended modification to the existing basal profiles.In this manner, the recommended modification to the basal profiles willbe a function of the actual measured glucose values of the patient underthe existing basal profiles.

In the manner described above, in accordance with the variousembodiments of the present invention, the patient and the doctor oreducator may work together to adjust the insulin profile to thepatient's activities. This will require experience and some trial anderror as well. An automated basal profile correction in accordance withthe embodiments of the present invention may monitor and gather muchmore information and may incorporate the knowledge of thephysician/educator within the modification algorithm. Indeed, differentobjectives can be identified and the modification algorithms developedto achieve the objectives.

Accordingly, a method in one embodiment includes monitoring an analytelevel of a patient, retrieving a predetermined parameter, anddetermining a modification to a drug therapy profile based on themonitored analyte level and the predetermined parameter.

The analyte includes glucose, and the drug infusion rate may include abasal profile.

Further, the predetermined parameter may include one or more of aninsulin sensitivity, a drug infusion rate, and a drug infusion timeperiod, a time period corresponding to the monitored analyte level, atime of day associated with the monitored analyte level, or a loop gainfactor.

Moreover, the monitoring step may include determining the analyte levelof the patient at a predetermined time interval including one of 5minutes, 30 minutes, 1 hour, or 2 hours.

The method in one embodiment may further include the step of outputtingthe modification to the drug therapy profile to the patient.

Also, the method may additionally include the step of implementing themodification to the drug therapy profile.

In a further aspect, the drug therapy profile may include an insulininfusion profile.

A system in yet another embodiment of the present invention includes ananalyte monitoring unit, and a processing unit operatively coupled tothe analyte monitoring unit, the processing unit configured to receive aplurality of monitored analyte levels of a patient, and to determine amodification to a drug therapy profile based on the received pluralityof monitored analyte levels.

The analyte monitoring unit in one embodiment may include a sensor unitprovided in fluid contact with an analyte of a patient.

Further, the sensor unit may include a subcutaneous analyte sensor, atranscutaneous analyte sensor, and a transdermal patch sensor.

Moreover, the processing unit may be operatively coupled to an infusiondevice.

In a further aspect, the processing unit may include an insulin pump.

Moreover, in still another aspect, the processing unit may be configuredto determine the modification based on a pattern in the monitoredanalyte level, where the pattern may be determined based on theplurality of monitored analyte levels for a predetermined time period,and further, where the predetermined time period may include one of a 12hour period, or 24 hour period.

The system in yet another embodiment may include a display unitoperatively coupled to the processing unit for displaying the determinedmodification.

Various other modifications and alterations in the structure and methodof operation of this invention will be apparent to those skilled in theart without departing from the scope and spirit of the invention.Although the invention has been described in connection with specificpreferred embodiments, it should be understood that the invention asclaimed should not be unduly limited to such specific embodiments. It isintended that the following claims define the scope of the presentinvention and that structures and methods within the scope of theseclaims and their equivalents be covered thereby.

What is claimed is:
 1. A method, comprising: monitoring an analyte levelof a patient; retrieving a predetermined parameter; and determining amodification to a drug therapy profile based on the monitored analytelevel and the predetermined parameter.